Inhibitory effect of galangin on DNA topoisomerases in lung cancer cells / 中南大学学报(医学版)
Journal of Central South University(Medical Sciences)
;
(12): 479-485, 2015.
Artigo
em Chinês
| WPRIM
| ID: wpr-815313
ABSTRACT
OBJECTIVE@#To explore the eff ect of galangin on DNA topoisomerases in lung cancer cells A549 and H46 as well on cell growth.@*METHODS@#The inhibitory effect of galangin on the growth of A549 and H46 cells was analyzed by MTT method. The effect of galangin on Topo I activity was detected by the agarose gel electrophoresis method. Furthermore, the interaction between galangin and Topo I was evaluated by fluorescence spectroscopy. Finally, the eff ect of galangin on the Topo I structure was discussed.@*RESULTS@#Galangin could induce the apoptosis of A549 and H46 cells (IC50 was 0.221 mmol/L and 0.173 mmol/L, respectively). Agarose gel electrophoresis showed that galangin exerted significant inhibitory effect on Topo I activity. Fluorescence spectrum analysis showed that galangin was able to quench Topo I fluorescence, and hydrophobic interaction was the main driving force. Circular dichroism analysis showed that galangin induced Topo I conformation change and increased the content of α-helix, which prevented the formation of active center and in turn led to the decrease in Topo I activity. Molecular simulation results showed that galangin could bind to the active center of Topo I to form hydrogen bonds with the catalytic site at Arg364 and Asn352.@*CONCLUSION@#Galangin is able to inhibit Topo I activity and to reduce the unwinding rate of single stranded DNNA in tumor cells, which plays an important role in induction of A549 and H46 cell apoptosis.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Flavonoides
/
Ciclo Celular
/
Química
/
Apoptose
/
DNA Topoisomerases Tipo I
/
Linhagem Celular Tumoral
/
Proliferação de Células
/
Inibidores da Topoisomerase
/
Neoplasias Pulmonares
/
Metabolismo
Limite:
Humanos
Idioma:
Chinês
Revista:
Journal of Central South University(Medical Sciences)
Ano de publicação:
2015
Tipo de documento:
Artigo
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